The research proposed in this competing renewal application for an ADAMHA Research Scientist Award is based on four grants currently funded by NIDA and NIAAA. The NIDA Clinical Research Center (DA- 04059) is concerned with polydrug abuse in women and its biological and behavioral antecedents and consequences. Polydrug use patterns of marihuana, alcohol and tobacco will be examined in clinical research ward studies using operant behavioral procedures. Drug interactions and covariance with premenstrual dysphoria will be assessed. New pharmacotherapies for cocaine, opiate and polydrug abuse will be evaluated in patients and in a primate drug self- administration model. The effects of abused substances on female reproductive function is a primary focus of this research. The consequences of chronic cocaine abuse will be examined in patients and in a primate model of drug abuse where polydrug use cannot influence data obtained (DA-04059). Parallel studies of alcohol's effects on reproductive function in women and in a primate model of alcoholism are continuing (AA-04368, AA-06252). The effects of acute alcohol intoxication are examined with provocative tests of pituitary, hypothalamic and ovarian function (LHRH, naloxone or hCG stimulation) in young and in post-menopausal women and in normal and ovariectomized monkeys. The effects of chronic alcohol dependence on the hypothalamic-pituitary-ovarian axis are examined in the monkey alcohol self-administration model and in alcoholic women during sobriety. The behavioral pharmacology of buprenorphine and other opioid mixed agonist-antagonist drugs will be studied in primates (DA-02519). This research is designed to evaluate the relative reinforcing efficacy (or potential abuse liability) of butorphanol, nalbuphine, pentazocine and buprenorphine relative to heroin. The effects of maintenance treatment with buprenorphine or naltrexone on the self- administration of commonly abused non-opioid drugs will also be examined. The overall objectives of the proposed research are to clarify the behavioral and biologic determinants and consequences of substance abuse and to improve understanding of the way in which drugs act as reinforcers, leading to their self-administration. Plans for professional growth include further study of neuroendocrinology, brain imaging and computer science.